Aggressive Tumor Cells Leave A Trail In Their Environment That Affects The Spread Of Cancer

The researchers found that aggressive melanoma cells lay down a molecular track as they interact with their extracellular matrix. These tracks appear to contain information and cues which, like bread crumbs on a path, contain information and directions that can be interpreted by less aggressive tumor cells. These cues may persist in the matrix long after the aggressive tumor cells have moved on and then cause less aggressive cells, which move into this area, to become more aggressive.

The UI team, led by Mary J.C. Hendrix, Ph.D., the Kate Daum Research Professor and head of anatomy and cell biology, and deputy director of the Holden Comprehensive Cancer Center at the UI, collaborated with researchers at the Scripps Research Institute in La Jolla, Calif., and researchers at the National Human Genome Institute and the National Cancer Institute, both parts of the National Institutes of Health, in Bethesda, Md.

Their research findings are reported in the Sept. 1 issue of the journal Cancer Research. Images from the study are featured on the cover of the journal.

"We wanted to know what these aggressive cancer cells were doing to their extracellular matrix environment," said Richard E. B. Seftor, Ph.D., a research scientist in Hendrix's laboratory and lead author of the paper. "We found that aggressive melanoma cells could alter their environment and cause other less aggressive melanoma cells to act more aggressively."

Similar to the example of remodeling your house, cells remodel their extracellular environment by both knocking down and building up the physical structure they live in. One of the fundamental building blocks of the extracellular matrix is produced by cells and is a family of proteins called laminins.

Other proteins produced by cells, called matrix metalloproteinases (MMPs), act to break down and remodel the extracellular matrix. The interplay of building up and breaking down the extracellular matrix by cells plays a major role in how wounds heal, how cancer spreads through the body (metastasis) and how the body deals with inflammation.

Certain members of the MMP family of proteins contribute to the aggressiveness of cancer cells. MMPs are important in helping tumor cells leave a primary tumor and move into and out of the body’s blood (and lymph) vessels. After entering these vessels, tumor cells can travel to distant parts of the body and begin growing in new tissues.

The ability to spread through the body and invade new tissues are two features that define a more aggressive and dangerous cancer. Furthermore, aggressive tumor cells can mimic other cell types, such as the cells that form vascular networks in the body (a process called vasculogenic mimicry), while less aggressive tumor cells do not form these networks.

"Our investigation aimed to define the intricate interactions between certain matrix metalloproteinases produced by the aggressive cancer cells, and a specific extracellular matrix molecule called laminin 5, gamma 2 chain," Hendrix said. "We found that this particular laminin is produced almost exclusively by aggressive, compared to poorly aggressive, melanoma cells. Furthermore, two specific MMPs (MMP-2 and MMP-14) wer